CN1314444C - Medicinal composition for treating diabetes and its complication and viral hepatitis and its preparation method - Google Patents
Medicinal composition for treating diabetes and its complication and viral hepatitis and its preparation method Download PDFInfo
- Publication number
- CN1314444C CN1314444C CNB031208029A CN03120802A CN1314444C CN 1314444 C CN1314444 C CN 1314444C CN B031208029 A CNB031208029 A CN B031208029A CN 03120802 A CN03120802 A CN 03120802A CN 1314444 C CN1314444 C CN 1314444C
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- China
- Prior art keywords
- alprostadil
- medicine
- cyclodextrin
- diabetes
- lecithin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000000203 mixture Substances 0.000 title claims abstract description 22
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 206010019799 Hepatitis viral Diseases 0.000 title claims abstract description 11
- 201000001862 viral hepatitis Diseases 0.000 title claims abstract description 11
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 claims abstract description 46
- 229960000711 alprostadil Drugs 0.000 claims abstract description 46
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims abstract description 46
- 239000003814 drug Substances 0.000 claims abstract description 43
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 26
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 20
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims abstract description 19
- 239000000787 lecithin Substances 0.000 claims abstract description 19
- 235000010445 lecithin Nutrition 0.000 claims abstract description 19
- 229940067606 lecithin Drugs 0.000 claims abstract description 19
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 16
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 15
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 13
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000002347 injection Methods 0.000 claims abstract description 13
- 239000007924 injection Substances 0.000 claims abstract description 13
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 13
- 229940046009 vitamin E Drugs 0.000 claims abstract description 13
- 239000011709 vitamin E Substances 0.000 claims abstract description 13
- 239000002502 liposome Substances 0.000 claims abstract description 12
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims abstract description 11
- 229930195725 Mannitol Natural products 0.000 claims abstract description 11
- 239000000594 mannitol Substances 0.000 claims abstract description 11
- 235000010355 mannitol Nutrition 0.000 claims abstract description 11
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 10
- 229940107161 cholesterol Drugs 0.000 claims abstract description 6
- 239000007788 liquid Substances 0.000 claims description 26
- 239000012047 saturated solution Substances 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 15
- 235000003969 glutathione Nutrition 0.000 claims description 15
- 229960003180 glutathione Drugs 0.000 claims description 15
- 239000008363 phosphate buffer Substances 0.000 claims description 14
- 229940119744 dextran 40 Drugs 0.000 claims description 10
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 claims description 8
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 238000005374 membrane filtration Methods 0.000 claims description 8
- 230000001954 sterilising effect Effects 0.000 claims description 8
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- 238000003756 stirring Methods 0.000 claims description 8
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 6
- 229960004756 ethanol Drugs 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 238000005360 mashing Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- 238000012856 packing Methods 0.000 claims description 4
- 238000000859 sublimation Methods 0.000 claims description 4
- 230000008022 sublimation Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 claims description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 abstract description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 9
- 239000008103 glucose Substances 0.000 abstract description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract description 8
- 102000004877 Insulin Human genes 0.000 abstract description 7
- 108090001061 Insulin Proteins 0.000 abstract description 7
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 abstract description 6
- 229940080345 gamma-cyclodextrin Drugs 0.000 abstract description 6
- 229940125396 insulin Drugs 0.000 abstract description 6
- 230000023852 carbohydrate metabolic process Effects 0.000 abstract description 4
- 206010008190 Cerebrovascular accident Diseases 0.000 abstract description 3
- 206010020772 Hypertension Diseases 0.000 abstract description 3
- 208000008589 Obesity Diseases 0.000 abstract description 3
- 208000006011 Stroke Diseases 0.000 abstract description 3
- 235000020824 obesity Nutrition 0.000 abstract description 3
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 abstract description 2
- 206010019280 Heart failures Diseases 0.000 abstract description 2
- 101000976075 Homo sapiens Insulin Proteins 0.000 abstract description 2
- 208000001647 Renal Insufficiency Diseases 0.000 abstract description 2
- 206010047115 Vasculitis Diseases 0.000 abstract description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 abstract description 2
- 208000029078 coronary artery disease Diseases 0.000 abstract description 2
- -1 dextranum-40 Chemical compound 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 abstract description 2
- 201000001881 impotence Diseases 0.000 abstract description 2
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 abstract description 2
- 201000006370 kidney failure Diseases 0.000 abstract description 2
- 208000033808 peripheral neuropathy Diseases 0.000 abstract description 2
- XYAUIVRRMJYYHR-UHFFFAOYSA-N acetic acid;propane-1,2,3-triol Chemical compound CC(O)=O.OCC(O)CO XYAUIVRRMJYYHR-UHFFFAOYSA-N 0.000 abstract 2
- 108010024636 Glutathione Proteins 0.000 abstract 1
- 206010061216 Infarction Diseases 0.000 abstract 1
- 206010022489 Insulin Resistance Diseases 0.000 abstract 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
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- 238000007710 freezing Methods 0.000 abstract 1
- 230000007574 infarction Effects 0.000 abstract 1
- 239000012466 permeate Substances 0.000 abstract 1
- 239000008055 phosphate buffer solution Substances 0.000 abstract 1
- 210000001147 pulmonary artery Anatomy 0.000 abstract 1
- 208000024891 symptom Diseases 0.000 abstract 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 abstract 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 abstract 1
- 210000004185 liver Anatomy 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
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Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a medicine for treating viral hepatitis, diabetes and complications thereof, and a preparation method for the medicine. The medicine of the present invention contains the following components of alprostadil, vitamin E, reduced glutathione, 2 hydroxypropyl-beta-cyclodextrin or gamma-cyclodextrin, fabaceous lecithin or lecithin, cholesterol or octadecanamine, dextranum-40, mannitol and phosphate buffer solution, can treat diabetes, regulate glycometabolism in a human body, stimulate glycometabolism, oxidize glucose and promote glucose and acetic acid to synthesize glycerine acetate. The medicine is the same as insulin, can make more glucose permeate into glycerine acetate, besides, promote glucose to synthesize glucogen, and treat human insulin resistance symptom, and high blood pressure, hyperlipoidemia, obesity, cerbral infarction, coronary heart disease, apoplexy, sequelae of apoplexy, angina pectoris, heart failure, pulmonary artery hypertension, kidney failure, vasculitis, peripheral neuropathy, diabetes sexual impotence, etc. caused by obesity factors. The medicine of the present invention is particularly prepared into a sterile freeze dried liposome injection on the basis of being prepared into liposome, so that the medicine has advanced progress and stability in a formulation, and availability extension, and overcomes the defect of freezing storage and transportation.
Description
Technical field
The present invention relates to a kind of composition of medicine and tool preparation method for the treatment of diabetes and complication and viral hepatitis.
Background technology
Known existing treatment of diabetes is based on hypoglycemic medicines such as insulins, the curative effect of this medicine only is to reduce the blood glucose of diabetes, keep not developing of the state of an illness, can not cure diabetes, complication such as the cardiovascular disease that more impossible treatment diabetes cause, nephropathy, oculopathy, the change of peripheral nerve sexually transmitted disease (STD) and arterial occlusive disease.Simultaneously because the excessive or long-time medication of insulin dose makes diabetics cause insulin accumulation reaction, the state of an illness of aggravation cardiovascular and cerebrovascular disease.
Summary of the invention
The objective of the invention is to overcome the above-mentioned shortcoming of prior art, a kind of composition of medicine for the treatment of diabetes and complication and viral hepatitis is provided.
The present invention also aims to provide the preparation method of composition of medicine of the present invention.
The present invention realizes by following component:
Alprostadil, vitamin E, reduced glutathion, 2 HP-or gamma-cyclodextrin, fabaceous lecithin or lecithin, cholesterol or 18-amine., low molecular dextran-40, mannitol, phosphate buffer;
The weight proportion of described raw material is:
Alprostadil 0.1g-0.4g
Vitamin E 0.5g-1.0g
Reduced glutathion 0.1g-0.2g
The 5-6 of 2 HP-or gamma-cyclodextrin Alprostadil molal quantity doubly
The 7-9 of fabaceous lecithin or lecithin Alprostadil molal quantity doubly
The 7-9 of cholesterol or 18-amine. Alprostadil molal quantity doubly
300 times of low molecular dextran-40 Alprostadil weight
200 times of mannitol Alprostadil weight
Phosphate buffer adds to volume 1000ml-2000ml
As content 〉=99.5% of optimizing described Alprostadil; The content of vitamin E 〉=95%; The content of reduced glutathion 〉=99%.
The preparation method of composition of medicine of the present invention may further comprise the steps:
A. the recipe quantity with Alprostadil is dissolved in the dehydrated alcohol, forms near saturated solution;
B. the recipe quantity with 2 HP-or gamma-cyclodextrin is dissolved in the phosphate buffer, forms near saturated solution;
C. the recipe quantity with glutathion is dissolved in the above-mentioned cyclodextrin near saturated solution, the dehydrated alcohol near saturated solution that drips Alprostadil again to the cyclodextrin near saturated solution, dissolving fully, cross degerming with membrane filtration after, make the lipidosome solid core liquid;
D. fabaceous lecithin or lecithin, cholesterol or 18-amine., vitamin E are formed near saturated solution with anhydrous alcohol solution; Phosphate buffer with remainder, low molecular dextran-40 and mannitol dissolving back merge with above-mentioned three's ethanol solution, after mixing was stirred and spared, steam sterilization was 10 minutes-30 minutes under 115 ℃ of-125 ℃ of conditions, and stir in tissue mashing machine under aseptic condition the sterilization back, ultrasonic echography 5 minutes-20 minutes 2 times, make empty liposome liquid, be cooled to room temperature, add the lipidosome solid core liquid that above-mentioned c made in the step, stir, make liquid drug;
E. liquid drug is used cillin bottle fill false add plug, every fill amount 1.0-2.0ml under aseptic condition;
F. with behind the liquid drug false add plug, cillin bottle send in the drying baker of lyophilization unit, and sublimation drying becomes aseptic freeze-dried liposome injection under-40 ℃-40 ℃, vacuum pressure 2.3Pa-50Pa condition, and tamponade under the vacuum is rolled lid under the aseptic condition, and packing is up to the standards.
As optimizing the used filter membrane of described membrane filtration is 0.22 μ m.
The operation of above-mentioned preparation method is all carried out under the aseptic condition of country's " Good Manufacturing Practice and Quality Control of Drug ".
Alprostadil is the endogenous substance that a kind of physiologically active is regulated the human body endocrine function widely, and it can treat diabetes, can regulate carbohydrate metabolism again in human body, stimulates carbohydrate metabolism and oxidizing glucose, and promotes glucose and acetic acid synthetic glycerine fat; The same with insulin, except that increase glucose infiltration glycerol fat, promote that also the synthetic bran of glucose is former, in addition, Alprostadil acts on also similar in the CAMP system to insulin, they all have inhibitory action to the accumulation of CAMP in the adipose cell, and more valuable is that Alprostadil possesses the treatment human insulin opposing disease that insulin does not possess, caused hypertension such as fat factor, hyperlipidemia, obesity, cerebral infarction, apoplexy and sequela thereof, coronary heart disease, angina pectoris, heart failure, pulmonary hypertension, renal failure, vasculitis, complication such as peripheral neuropathy and diabetes sexual impotence.Reduced glutathion is a kind of antioxidant of effective anti-photooxidation, is furnished with reduced glutathion in this composition of medicine, is subjected to the rotten disadvantage of losing drug effect after the photooxidation in order to overcome Alprostadil in the common injection of Alprostadil.Glutathion protects the human liver to avoid entering medicine infringement human liver anti-allergic effects in the liver in addition simultaneously.Alprostadil has good curing viral hepatitis curative effect, the critically ill patient survival rate is 81.5%, chronic hepatitis and patient with liver cirrhosis treatment improvement rate are 71.0%, and be embodied in following aspects: 1. Alprostadil has protective effect to hepatocyte, organelle; 2. Alprostadil can prevent the hepatocyte fatty infiltration, reduces the acetic acid glyceride and soaks in liver; 3. Alprostadil has the effect of intensive blood vessel dilating and anticoagulant, can make the popular feeling, kidney, liver blood vessel expansion, improves the microcirculation of liver; 4. the hepatocellular substance metabolism of Alprostadil scalable; 5. Alprostadil has immunoregulation effect, and the immunity damage that evokes behind the hepatites virus infections is had certain inhibitory action, thus the development of disease controlling.6. fabaceous lecithin and a small amount of cholesterol mate, the Alprostadil composition of medicine is made Liposomal formulation earlier, the Alprostadil composition of medicine is made had the preparation that slow release has controlled release again and targeting is more arranged, this composition of medicine is made the targeting agent that concentrates on blood of human body circulation and the distribution of liver system, make this medicine on dosage form, have more advance, more valuable is composition of medicine of the present invention to be made the aseptic freeze-dried injection of making liposome on the liposome basis again, make composition of medicine of the present invention have more stability, the refrigerator storing is got rid of in extension of validity.
The specific embodiment
The present invention treats the composition of medicine of diabetes and complication and viral hepatitis and is made by the components in portion by weight of the following example:
Embodiment 1
Alprostadil content 〉=99.5% 0.1g-0.2g
Vitamin E content 〉=95% 0.5g-0.8g
Reduced glutathion content 〉=99% 0.1g
6 times of 2 HP-content, 99% Alprostadil molal quantity
The fabaceous lecithin injection is with 9 times of the Alprostadil molal quantity
The cholesterol injection is with 9 times of the Alprostadil molal quantity
Low molecular dextran-40 injection 30g
Mannitol 20g
Phosphate buffer 0.01M PH7.0 adds to 1000ml
Be distributed into 1000
The preparation method of composition of medicine of the present invention is as follows:
1. the 0.1g-0.2g Alprostadil is dissolved in the 3ml dehydrated alcohol, forms near saturated solution;
2. 2 HP-are dissolved in the 12ml phosphate buffer, form near saturated solution;
3. glutathion 0.1g is dissolved in nearly saturated the making in the solution of 2 step cyclodextrin, the dehydrated alcohol near saturated solution of the Alprostadil that 1 step was made drops to above-mentioned making in the near saturated solution again, dissolving fully, cross degerming with membrane filtration after, make the lipidosome solid core liquid;
4. with fabaceous lecithin, cholesterol, vitamin E forms near saturated solution with anhydrous alcohol solution, 988ml phosphate buffer with remainder, low molecular dextran-40 and mannitol dissolving back merge with above-mentioned three's ethanol solution, after stirring is even, steam sterilization under 115 ℃ of-120 ℃/10 minutes-30 minutes conditions, stirred 10 minutes in tissue mashing machine under aseptic condition the sterilization back, ultrasonic echography 5 minutes-10 minutes 2 times, make empty liposome liquid, be cooled to room temperature, add the lipidosome solid core liquid (is 0.22 μ m membrane filtration lipidosome solid core liquid later with filter membrane) that makes in above-mentioned 3 steps, stir, make liquid drug;
5. liquid drug is used 2.0ml cillin bottle fill false add plug, every fill amount 1.0-2.0ml under aseptic condition;
6. the cillin bottle behind the liquid drug false add plug is sent in the drying baker of lyophilization unit, sublimation drying becomes aseptic freeze-dried liposome injection under-40 ℃-40 ℃, vacuum pressure 2.3Pa-50Pa condition, roll lid under the tamponade under the vacuum, aseptic condition, packing is up to the standards.
Embodiment 2
Alprostadil content 〉=99.5% 0.2g-0.4g
Vitamin E content 〉=95% 0.8g-1.0g
Reduced glutathion content 〉=99% 0.2g
5 times of gamma-cyclodextrin content 〉=99% Alprostadil molal quantity
The lecithin injection is with 7 times of the Alprostadil molal quantity
The 18-amine. injection is with 7 times of the Alprostadil molal quantity
Low molecular dextran-40 injection 30g
Mannitol 20g
Phosphate buffer 0.01M PH7.0 adds to 1000ml
Be distributed into 1000
The preparation method of composition of medicine of the present invention:
1. the 0.2g-0.4g Alprostadil is dissolved in the 3ml dehydrated alcohol, forms near saturated solution;
2. gamma-cyclodextrin is dissolved in the 12ml phosphate buffer, forms near saturated solution;
3. glutathion 0.2g is dissolved in nearly saturated the making in the solution of 2 step cyclodextrin, the dehydrated alcohol near saturated solution of the Alprostadil that 1 step was made drops to above-mentioned making in the near saturated solution again, dissolving fully, cross degerming with membrane filtration after, make the lipidosome solid core liquid;
4. with lecithin, 18-amine., vitamin E forms near saturated solution with anhydrous alcohol solution, 988ml phosphate buffer with remainder, low molecular dextran-40 and mannitol dissolving back merge with above-mentioned three's ethanol solution, after stirring is even, steam sterilization under 120 ℃ of-125 ℃/15 minutes conditions, stirred 10 minutes in tissue mashing machine under aseptic condition the sterilization back, ultrasonic echography 10 minutes-20 minutes 2 times, make empty liposome liquid, be cooled to room temperature, add the lipidosome solid core liquid (is 0.22 μ m membrane filtration lipidosome solid core liquid later with filter membrane) that makes in above-mentioned 3 steps, stir, make liquid drug;
5. liquid drug is used 2.0ml cillin bottle fill false add plug, every fill amount 1.0-2.0ml under aseptic condition;
6. the cillin bottle behind the liquid drug false add plug is sent in the drying baker of lyophilization unit, sublimation drying becomes aseptic freeze-dried liposome injection under-40 ℃-40 ℃, vacuum pressure 2.3Pa-50Pa condition, roll lid under the tamponade under the vacuum, aseptic condition, packing is up to the standards.
Claims (4)
1. preparation method for the treatment of the composition of medicine of diabetes and complication and viral hepatitis is characterized in that may further comprise the steps:
A. the recipe quantity with Alprostadil is dissolved in the dehydrated alcohol, forms near saturated solution;
B. the recipe quantity with 2 HP-or Y-cyclodextrin is dissolved in the phosphate buffer, forms near saturated solution;
C. the recipe quantity with glutathion is dissolved in the above-mentioned cyclodextrin near saturated solution, the dehydrated alcohol near saturated solution that drips Alprostadil again to the cyclodextrin near saturated solution, dissolving fully, cross degerming with membrane filtration after, make the lipidosome solid core liquid;
D forms near saturated solution with fabaceous lecithin or lecithin, cholesterol or 18-amine., vitamin E with anhydrous alcohol solution; Phosphate buffer with remainder, low molecular dextran-40 and mannitol dissolving back merge with above-mentioned three's ethanol solution, after mixing was stirred and spared, steam sterilization was 10 minutes-30 minutes under 115 ℃ of-125 ℃ of conditions, and stir in tissue mashing machine under aseptic condition the sterilization back, ultrasonic echography 5 minutes-20 minutes 2 times, make empty liposome liquid, be cooled to room temperature, add the lipidosome solid core liquid that above-mentioned c made in the step, stir, make liquid drug;
E. liquid drug is used cillin bottle fill false add plug under aseptic condition, every fill amount 1.0-2.0ml:
F. with behind the liquid drug false add plug, cillin bottle send in the drying baker of lyophilization unit, and sublimation drying becomes aseptic freeze-dried liposome injection under-40 ℃-40 ℃, vacuum pressure 2.3Pa-50Pa condition, and tamponade under the vacuum is rolled lid under the aseptic condition, and packing is up to the standards.
2. a kind of preparation method for the treatment of the composition of medicine of diabetes and complication and viral hepatitis according to claim 1 is characterized in that: the used filter membrane of membrane filtration is 0.22um.
3. with the treatment diabetes of the described preparation method preparation of claim 1 and the composition of medicine of complication and viral hepatitis thereof, it is characterized in that this composition of medicine includes following component:
Alprostadil, vitamin E, reduced glutathion, 2 HP-or Y-cyclodextrin, fabaceous lecithin or lecithin, cholesterol or 18-amine., low molecular dextran-40, mannitol, phosphate buffer;
The weight proportion of described raw material is:
Alprostadil 0.1g-0.4g
Vitamin E 0.5g-1.0g
Reduced glutathion 0.1g-0.2g
The 5-6 of 2 HP-or v-cyclodextrin Alprostadil molal quantity doubly
The 7-9 of fabaceous lecithin or lecithin Alprostadil molal quantity doubly
The 7-9 of cholesterol or 18-amine. Alprostadil molal quantity doubly
300 times of low molecular dextran-40 Alprostadil weight
200 times of mannitol Alprostadil weight
Phosphate buffer adds to volume 1000ml-2000ml.
4. the composition of medicine of treatment diabetes according to claim 3 and complication and viral hepatitis is characterized in that: the content of described Alprostadil 〉=99.5%; The content of vitamin E 〉=95%; The content of reduced glutathion 〉=99%.
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| CA2547934C (en) | 2004-02-19 | 2013-05-21 | Abbott Laboratories | Methods of using gamma cyclodextrin to control blood glucose and insulin secretion |
| CN1895671B (en) * | 2005-12-08 | 2012-11-28 | 淮北辉克药业有限公司 | Compound preparation for treating viral liver disease |
| CN1915222B (en) * | 2006-09-18 | 2010-08-04 | 蔡海德 | Composition of liposome, and preparation method |
| ITCA20080017A1 (en) * | 2008-07-31 | 2010-02-01 | Giuseppe Brotzu | PHARMACY BASED ON PHOSPHATIDYLCOLINE LIPOSOMAS TRANSPORTING A PROSTAGLANDINE E1 LINKED TO ALPHA-CYCLODESTRINE FOR THE TREATMENT OF DIABETIC MICRONGIOPATHIES AND OTHER VASCULAR DISEASES. |
| CN101843594B (en) * | 2010-05-11 | 2011-05-25 | 重庆药友制药有限责任公司 | Alprostadil freeze-dried emulsion for injection and preparation method thereof |
| CN102018672B (en) * | 2010-11-29 | 2013-09-18 | 广州朗圣药业有限公司 | Freeze-dried liposome composition of water-soluble medicament and preparation method thereof |
| CN102100904B (en) * | 2011-01-25 | 2013-04-24 | 成都卓阳生物科技有限公司 | Reduced glutathione percutaneous absorption preparation and preparation method thereof |
| CN102274184B (en) * | 2011-07-28 | 2013-05-08 | 蔡海德 | Alprostadil liposome composite medicine and industrial preparation, quality control and use |
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Correction item: Denomination of Invention Correct: Combined medicine for treating diabetes and its complication and viral hepatitis and preparation method thereof False: Combined medicine for treating corn urine disease and its complication and viral hepatitis and preparation method thereof Number: 19 Page: The title page Volume: 23 |
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Free format text: CORRECT: INVENTION NAME; FROM: A COMBINED MEDICINE FOR THE TREATMENT OF URINE DISEASE OF CHAFF AND ITS COMPLICATION AND VIRUS HEPATITIS AND ITS PREPARATION METHOD TO: A TREATMENT FOR DIABETES AND ITS COMPLICATIONS AND THE COMBINATION OF VIRAL DRUGS AND THEIR PREPARATION METHODS |
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